SRGAP2 is a postsynaptic RAC1 GTPase activating protein that plays a crucial role in neuronal development and synaptic regulation. The protein functions by binding and deforming membranes to regulate actin dynamics, controlling cell migration and differentiation 1. SRGAP2A promotes synaptic maturation by interacting with key postsynaptic scaffolding proteins Homer (at excitatory synapses) and Gephyrin (at inhibitory synapses), while simultaneously limiting synaptic density through its RAC1-GAP activity 1. Mechanistically, SRGAP2A promotes the accumulation of AMPA and GABAA receptors at synapses, coordinating the balanced development of both excitatory and inhibitory synapses 1. The gene has particular evolutionary significance in humans due to human-specific duplications SRGAP2B/C, which antagonize SRGAP2A function and contribute to synaptic neoteny - the extended period of synaptic maturation characteristic of human neurons 2. This neotenic regulation involves modulation of SYNGAP1 levels, linking SRGAP2 to intellectual disability and autism spectrum disorders 2. SRGAP2 is also expressed in microglia, where human-specific paralogs induce neotenic features of microglial maturation that non-cell autonomously impact synaptic development 3. Loss of SRGAP2 function is associated with altered excitatory/inhibitory neuron balance and increased seizure susceptibility 4.