PTHLH (parathyroid hormone-like hormone) is a hormone that activates G protein-coupled receptor signaling pathways and regulates skeletal development and bone resorption. Functionally, PTHLH plays critical roles in osteoblast differentiation and skeletal system development through reciprocal regulation with Runx2 and other signaling molecules 1 2. During development, PTHLH is essential for mammary gland morphogenesis and embryonic nipple formation 3 4. PTHLH regulates chondrocyte differentiation and osteoblast development, negatively controlling cell proliferation in these lineages 1. Beyond normal physiology, PTHLH is frequently amplified in pancreatic cancer as part of the KRAS amplicon, where it drives tumor growth and metastasis by promoting epithelial-to-mesenchymal transition and upregulating osteopontin (Spp1) 5. In renal cell carcinoma, HIF-2-dependent PTHLH expression drives paraneoplastic hypercalcemia, representing a therapeutic vulnerability 6. Additionally, PTHLH expression may contribute to pluripotency maintenance and genomic integrity in induced pluripotent stem cells through interactions with cell cycle regulators 7. Clinically, PTHLH mutations are associated with Brachydactyly E2. The gene demonstrates widespread tissue expression with variant-dependent patterns, suggesting complex regulatory mechanisms controlling its diverse developmental and pathological functions.