Indian hedgehog homolog (IHH)

Indian hedgehog homolog (IHH) is a secreted morphogen in the Hedgehog signaling pathway, one of three mammalian Hedgehog proteins along with Sonic hedgehog (SHH) and Desert hedgehog (DHH)[3][2][1]. IHH is essential for regulating chondrocyte differentiation, proliferation, and maturation during endochondral ossification, thereby orchestrating limb and bone development[3][4]. It signals through binding the Patched (PTCH) receptor, relieving inhibition on Smoothened (SMO), and activating nuclear Gli transcription factors that regulate target genes for cell proliferation and differentiation[1][2]. IHH is also implicated in feedback regulation of parathyroid hormone-related peptide, bone homeostasis, and endometrial function[3]. Mutations in *IHH* cause skeletal disorders (e.g., brachydactyly type A1); aberrant signaling plays a role in cancer and other diseases[3][1][4]. IHH is considered a therapeutic target, and pathway inhibitors are used in cancers where Hedgehog signaling is dysregulated[1]. Safety concerns surround the risk of interfering with normal developmental or bone homeostasis when the pathway is inhibited.

Other names

Indian hedgehogIHHIhh protein

Direct inhibition of Hedgehog pathway downstream of IHH ligand by antagonizing SMO receptor (blocking signal transduction)