INSC is a spindle orientation adaptor protein that functions as a critical link between the Par3 complex and the GPSM1/GPSM2 complex, regulating asymmetric cell division during nervous system development. The protein localizes to the apical cell cortex during mitosis and orients the spindle along the apical-basal axis, with evolutionary conservation across species from Drosophila to humans 1. Beyond its developmental role, INSC has emerged as clinically significant in two distinct disease contexts. A missense mutation (Met70Arg) in INSC was identified in patients with axonal Charcot-Marie-Tooth disease type 2 (CMT2), where the mutation impairs the PAR3/INSC/LGN complex function in the peripheral nervous system, causing tubulin aggregation and neurodegeneration; microtubule-stabilizing agents rescued cellular defects in models of this mutation 2. In colon adenocarcinoma, INSC is significantly downregulated and serves as an independent prognostic factor—patients with lower INSC expression have shorter overall survival and increased tumor stage 3. INSC downregulation correlates with altered immune infiltration patterns, negatively associating with B cells, CD4+ T cells, and dendritic cells 4. Genome-wide association studies have also linked INSC variants to cognitive processing speed and Alzheimer's disease-related phenotypes 5, suggesting broader neurological relevance.