PTHrP (Parathyroid Hormone-Related Protein): The Tumour Factor Behind Cancer's High Calcium — and the Template for Abaloparatide

Parathyroid hormone-related protein is a 139-to-173-amino-acid protein, found in 1987 as the factor some cancers release to raise blood calcium. It shares its opening stretch with parathyroid hormone, works through the same receptor, and is the model for the osteoporosis drug abaloparatide.

Made by the body139–173 amino acids — a proteinIts 1–34 region is copied by an approved drug

Caroline S · Published 2026-10-27

Length

Three forms from one gene: 139, 141 or 173 amino acids after a 36-residue signal and pro sequence is removed (UniProt P12272 isoforms 2, 1 and 3; Suva et al. 1987 reported the 141-residue form). All are well over the 40-residue line US regulation uses for proteins (21 CFR 600.3).

Sequence

Isoform 1 precursor 177 residues (UniProt P12272); signal 1–24, pro sequence 25–34, mature chain 37–177; cut into PTHrP[1-36], PTHrP[38-94] and osteostatin (precursor 143–175)

Origin

Made in many tissues during development and in adult life; first purified from a human lung cancer cell line (Moseley et al., PNAS 1987, PMID 2885845) and cloned the same year (Suva et al., Science, PMID 3616618). UniProt places it in the parathyroid hormone family.

Last reviewed

2026-10-27

What is it good for?

In the body, UniProt's annotation describes a regulator of cell and organ growth and development — including bone development — and of calcium transport across epithelia, acting through the PTH1R receptor it shares with parathyroid hormone. In medicine, it matters two ways: some cancers release it and push blood calcium dangerously high, and its first 34 residues were the template for abaloparatide (Tymlos), an approved osteoporosis drug. PTHrP itself is not a medicine.

Illustration: A clear glass Erlenmeyer flask with pale green liquid, a white stirring rod, on a light wooden surface. — Illustration

What it is

Parathyroid hormone-related protein — PTHrP — is a protein whose opening stretch looks like parathyroid hormone. It is made from its own gene (PTHLH), and UniProt's record (P12272) lists three forms produced by alternative splicing:

Form (UniProt)	Precursor	After the 36-residue signal and pro sequence
Isoform 2	175	139
Isoform 1	177	141
Isoform 3	209	173

Mature lengths counted by this library from UniProt's isoform sequences and its signal (1–24) and pro (25–34) annotations; Suva et al. (1987) reported a 36-residue prepro sequence and a 141-residue mature protein.

Every form is a protein, three to four times the 40-residue line US regulation uses (21 CFR 600.3; see peptide versus protein). The library carries it because readers meet it as a blood test in cancer care, and because the approved osteoporosis drug abaloparatide was built from its first 34 residues.

How it was found

PTHrP was found by chasing a symptom. Some cancers raise blood calcium without spreading to bone — a condition called humoral hypercalcemia of malignancy — and in 1987 two papers identified the factor behind many cases.

Moseley and colleagues (PNAS, PMID 2885845) purified an 18-kDa protein from a human lung cancer cell line that acted like parathyroid hormone. 8 of its first 16 residues were identical to parathyroid hormone's, yet the cells carried no parathyroid-hormone message — "indicating involvement of another gene".
Suva and colleagues (Science, PMID 3616618) cloned that gene, describing a prepro sequence of 36 amino acids and a mature protein of 141 with "significant homology with parathyroid hormone in the amino-terminal region", and suggested it "may be important in normal as well as abnormal calcium metabolism".

What it does

UniProt's annotation describes PTHrP as a regulator of cell and organ growth, development, migration, differentiation and survival, and of calcium transport across epithelia — including endochondral bone development, the process by which cartilage is replaced with bone in the growing skeleton. It acts by binding PTH1R, the receptor it shares with parathyroid hormone.

The protein is also cut into pieces with names of their own. UniProt annotates PTHrP[1-36], the part that resembles parathyroid hormone; PTHrP[38-94]; and osteostatin, from the far end, described in laboratory studies as a potent inhibitor of osteoclasts, the cells that break down bone.

What is described	How firm
Released by some tumours, raising blood calcium	Human tumour cells and clinical syndrome (1987 papers)
Shares the PTH1R receptor with parathyroid hormone	UniProt annotation
Regulates bone development and epithelial calcium transport	UniProt annotation, largely from animal and cell work
Osteostatin inhibits bone breakdown	Laboratory studies; no human treatment trial found

The blood test

Because a tumour releasing PTHrP is a recognised cause of high blood calcium — the syndrome the 1987 papers set out to explain — PTHrP is measured as a blood test when that cause is being looked for. Laboratories set their own reference ranges. What a reading means for any one person is for the clinician who ordered it; this entry does not interpret results.

The drug modelled on it

Abaloparatide is a synthetic 34-amino-acid analogue of PTHrP(1-34), sharing 76% of that sequence (and 41% of parathyroid hormone's 1–34, per its label). FDA application data list it as Tymlos, NDA208743, approved 2017-04-28 for osteoporosis. Its fracture trial and warnings are in its own entry. Teriparatide, the older bone-building drug, copies parathyroid hormone instead. PTHrP itself has never been approved as a medicine.

Where it stands

Not a medicine; the template for one approved drug.
Published record: PubMed returns 5,370 records for PTHrP or parathyroid hormone-related protein, 40 tagged as randomised controlled trials; ClinicalTrials.gov lists 163 studies under the full name and 27 under "PTHrP" (all 2026-10-27).

Calcitonin is the thyroid hormone on the other side of calcium control, and parathyroid hormone the relative PTHrP was named after.

What the research shows

Tumours that release it cause high blood calcium

Moseley 1987 (PMID 2885845) purified it from a human lung cancer cell line; Suva 1987 (PMID 3616618) cloned it as 'a putative hypercalcemia factor' in humoral hypercalcemia of malignancy

Acts through the same receptor as parathyroid hormone

UniProt P12272 function annotation (PTH1R); Suva 1987 reported 'significant homology with parathyroid hormone in the amino-terminal region'

Its 1–34 region can be turned into a bone-building drug

Abaloparatide, a 34-amino-acid analogue sharing 76% of PTHrP(1-34), approved as Tymlos (NDA208743) on 2017-04-28 per FDA application data

Its C-terminal fragment osteostatin blocks bone loss in people

UniProt annotates osteostatin as a potent inhibitor of osteoclastic bone resorption from laboratory studies; this library found no human treatment trial of it

Bars show how much of the evidence is in humans, not how well anything works.

Where it stands

In the body

A protein in the parathyroid hormone family (UniProt), made in many tissues.

As a medicine

PTHrP is not a medicine. Abaloparatide (Tymlos), modelled on its first 34 residues, is approved for osteoporosis; teriparatide copies parathyroid hormone instead.

Published record

PubMed returns 5,370 records for PTHrP or parathyroid hormone-related protein, 40 tagged as randomised controlled trials; ClinicalTrials.gov lists 163 studies under the full name (2026-10-27).

Peptide Lexicon facts

UniProt gives three forms of human PTHrP from one gene, with precursors of 175, 177 and 209 residues; after the 36-residue signal and pro sequence they are 139, 141 and 173 amino acids long (P12272 isoforms 2, 1, 3).
PTHrP was purified in 1987 from a human lung cancer cell line as an 18-kDa protein whose first 16 residues matched parathyroid hormone at 8 positions (Moseley et al., PNAS, PMID 2885845).
The same year it was cloned as a putative factor in humoral hypercalcemia of malignancy, encoding a 36-residue prepro sequence and a 141-amino-acid mature protein (Suva et al., Science, PMID 3616618).
UniProt annotates three fragments of PTHrP: PTHrP[1-36], PTHrP[38-94] and osteostatin, the last described as a potent inhibitor of osteoclastic bone resorption in laboratory studies.
Abaloparatide, the osteoporosis drug Tymlos (NDA208743, approved 2017-04-28), is a 34-amino-acid analogue sharing 76% of its sequence with PTHrP(1-34).
PubMed returns 5,370 records for PTHrP or parathyroid hormone-related protein, 40 tagged as randomised controlled trials (2026-10-27).

Frequently asked questions

What is PTHrP?

Parathyroid hormone-related protein: a protein of 139 to 173 amino acids, depending on the form, whose opening stretch resembles parathyroid hormone and works through the same receptor. It was discovered in 1987 as the factor some cancers release to raise blood calcium.

What does a high PTHrP level mean?

It is measured when a tumour is being considered as the cause of high blood calcium, because PTHrP released by a tumour is one recognised cause — the 'humoral hypercalcemia of malignancy' the 1987 papers set out to explain. What a result means for one person is for the clinician who ordered it; this entry does not interpret results.

How is PTHrP different from parathyroid hormone?

They are made from different genes. Parathyroid hormone is an 84-amino-acid hormone of the parathyroid glands that sets blood calcium. PTHrP is longer, made in many tissues, and resembles parathyroid hormone only at its beginning — the 1987 purification found 8 of its first 16 residues identical. Both act on the PTH1R receptor.

Is abaloparatide the same as PTHrP?

No. Abaloparatide is a synthetic 34-amino-acid peptide modelled on PTHrP's first 34 residues, sharing 76% of that sequence. It is approved for osteoporosis as Tymlos. PTHrP itself is not a medicine.

What is osteostatin?

A fragment from the far end of PTHrP (precursor residues 143–175 in UniProt). Laboratory studies describe it as an inhibitor of the cells that break down bone; this library found no human treatment trial.