Human-specific protein that acts as a key modifier of cortical connectivity in the human brain (PubMed:22559944, PubMed:27373832, PubMed:34707291). Acts by inhibiting the functions of ancestral paralog SRGAP2/SRGAP2A, a postsynaptic protein that regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832). SRGAP2C is unstable but is able to heterodimerize with SRGAP2/SRGAP2A, thereby reducing SRGAP2/SRGAP2A levels through proteasome-dependent degradation (PubMed:27373832, PubMed:28333212, PubMed:31822692). Inhibition of SRGAP2/SRGAP2A by SRGAP2C leads to an increase in synaptic density and protracted synaptic maturation of both excitatory and inhibitory synapses (PubMed:27373832, PubMed:34707291). Modifies cortical circuit connectivity by increasing the number of local and long-range cortical inputs received by layer 2/3 pyramidal neurons (PubMed:34707291). Also able to increase the probability of sensory-evoked responses by layer 2/3 pyramidal neurons (PubMed:34707291). Homodimer (PubMed:22559944). Interacts (via F-BAR domain) with SRGAP2/SRGAP2A (via F-BAR domain); formation of the heterodimer inhibits SRGAP2/SRGAP2A function (PubMed:22559944, PubMed:28333212, PubMed:34707291). Ubiquitously expressed with higher expression in cerebellum (PubMed:22559943, PubMed:22559944). Probably expressed in fetal and adult neurons (at protein level) (PubMed:22559943). SRGAP2C is truncated at its C-terminus compared to SRGAP2/SRGAP2A (PubMed:28333212). It only contains an extended F-BAR domain that lacks the last C-terminal 49 amino acids of SRGAP2/SRGAP2A, which are replaced with seven unique C-terminal amino acids (PubMed:28333212). In addition, SRGAP2C acquired a series of unique nonsynonymous base pair mutations selectively targeting five arginine residues compared to SRGAP2B (PubMed:28333212). This truncation and these specific arginine mutations reduce solubility of SRGAP2C and increase its ability to heterodimerize with SRGAP2/SRGAP2A to form an insoluble complex (PubMed:28333212). This is one of the 3 duplications of the ancestral gene SRGAP2/SRGAP2A which has undergone human-specific segmental gene duplications (PubMed:22559944, PubMed:22559943). The appearance of SRGAP2C in the human genome is estimated to 2,4 million years and corresponds to the beginning of neocortex expansion in human evolution (PubMed:22559944, PubMed:22559943, PubMed:34707291). The emergence of SRGAP2C at the birth of the Homo lineage probably contributed to the evolution of specific structural and functional features of cortical circuits in the human cortex (PubMed:34707291). Expression of SRGAP2C in mouse cortical pyramidal neurons leads to the emergence of human-specific traits of synaptic development, characterized by increases in the density of both excitatory and inhibitory synapses received by layer 2/3 pyramidal neurons and neotenic features of excitatory and inhibitory synaptic development (PubMed:22559944, PubMed:27373832, PubMed:34707291). Mice humanized for SRGAP2C expression in all cortical pyramidal neurons show a shift in the fraction of layer 2/3 pyramidal neurons activated by sensory stimulation and an enhanced ability to learn a cortex-dependent sensory-discrimination task (PubMed:34707291).