INSC (Inscuteable Spindle Orientation Adaptor Protein) is a conserved adapter protein that links the Par3 complex to the GPSM1/GPSM2 complex 1, functioning as a critical regulator of asymmetric cell division and spindle orientation during mitosis 2. The protein contains an evolutionarily conserved ISH domain and C-terminal PDZ-binding motif 2, and is expressed broadly in tissues including eye, kidney, skin, and tumors 2. INSC plays essential roles in the developing nervous system, where it regulates neural progenitor cell proliferation and differentiation during asymmetric division 3. Beyond development, INSC maintains critical post-developmental functions in the adult peripheral nervous system (PNS). A missense mutation (p.Met70Arg) in INSC causes axonal Charcot-Marie-Tooth disease (CMT2), leading to proprioceptive defects and neurodegeneration through tubulin aggregation and microtubule dysfunction 4. Microtubule-stabilizing agents rescue these defects, revealing a therapeutic target 4. Genome-wide association studies identified INSC variants (rs1108010) associated with cognitive processing speed and Alzheimer's disease-related phenotypes, including Trail Making Test performance and cognitive decline measures 5. In colon cancer, INSC expression is significantly downregulated and correlates with worse prognosis and reduced immune infiltration 36, suggesting tumor-suppressive functions. INSC represents a multi-system regulator with disease relevance spanning neurodegenerative conditions, cognitive impairment, and cancer progression.