ITPR1 encodes inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), a ligand-gated calcium channel located on the endoplasmic reticulum membrane that mediates calcium release into the cytoplasm upon IP3 binding 1. The receptor undergoes conformational changes to transition from closed to open states, allowing calcium ion transfer across the ER membrane. Cytoplasmic calcium released by ITPR1 triggers apoptosis through CAMK2 complex activation and regulates diverse cellular processes including fertilization, secretion, and mitochondrial calcium-dependent apoptosis 2. ITPR1 functions as part of a multi-protein complex with HSPA9 and VDAC1 that facilitates calcium transport from the ER to mitochondria, providing substrate for the MCU channel 3. Pathogenic missense variants in ITPR1 cause autosomal dominant spinocerebellar ataxia types 15 and 29 (SCA15/SCA29), Gillespie syndrome, and pontocerebellar hypoplasia 1. Variants cluster in functionally critical domains: the N-terminal IP3-binding domain, the CA8-binding region, and the transmembrane channel domain 1. Clinical presentations show extreme phenotypic heterogeneity, ranging from infantile-onset ataxia with intellectual disability to late-onset pure cerebellar ataxia, with cerebellar atrophy observed across phenotypes but not correlating with symptom progression 45. ITPR1 also functions as a hub gene in medulloblastoma metastasis pathways 6.