IHH (Indian hedgehog signaling molecule) is a morphogen that plays essential roles in skeletal development and tissue homeostasis. As part of the Hedgehog signaling pathway, IHH binds to the PTCH1 receptor and activates downstream transcription through GLI transcription factors 1. In skeletal development, IHH regulates chondrocyte proliferation, differentiation, and endochondral bone formation, particularly impacting cranial bone development and temporomandibular joint formation 1. Loss of IHH function results in cranial bone malformation and decreased ossification 1. Pathogenic variants in IHH cause autosomal-dominant short stature with nonspecific skeletal abnormalities, including shortening of the middle phalanx of the fifth finger 2. Patients with IHH mutations show good response to growth hormone therapy 2. Beyond skeletal function, IHH expression increases during osteoarthritis progression, correlating with cartilage hypertrophy markers 3. Recent studies reveal that TNF-activated renal epithelial cells release IHH, which drives Gli1+ cell proliferation and contributes to organ fibrosis in kidney and heart tissues 4. IHH is located on chromosome 2 and represents an important therapeutic target for skeletal disorders and fibrotic diseases 5.