SRGAP1 (SLIT-ROBO Rho GTPase activating protein 1) is a GTPase-activating protein that inactivates RhoA and Cdc42 small GTPases, functioning downstream of SLIT-ROBO signaling 1. During neocortical development, SRGAP1 is highly expressed anteriorly between 8-12 postconceptional weeks and becomes confined to Layer V by 15 weeks, with prominent expression in corticospinal projection neurons 2. SRGAP1 functions as a key regulator of neuronal and epithelial biology: in neurons, neuronal Slit1 activates Robo2-SRGAP1-RhoA signaling to promote oligodendrocyte differentiation and myelination, particularly under hypoxic conditions 3. In podocytes, SRGAP1 localizes to foot processes and controls actin cytoskeleton dynamics by suppressing Rho GTPase activity, maintaining podocyte architecture and preventing foot-process effacement characteristic of focal segmental glomerulosclerosis 4. In epithelia, SRGAP1 actively suppresses RhoA signaling at junctions to maintain low contractility in developing monolayers, with recruitment modulation controlling the transition to mature contractile junctions 5. Clinically, SRGAP1 dysregulation is implicated in cancer pathology: overexpression occurs in gastric cancer through downregulation of tumor-suppressive miRNAs (miR-340, miR-124), promoting cell proliferation and Wnt/β-catenin pathway activation 1. Germline SRGAP1 variants (Q149H, A275T, R617C) impair CDC42 inactivation and are associated with papillary thyroid carcinoma susceptibility 6, with SRGAP1 identified as a low-penetrant modifier gene in familial non-medullary thyroid cancer 7.