KCTD13 encodes a substrate-specific adapter for the BCR(BTB-CUL3-RBX1) E3 ubiquitin ligase complex located on chromosome 16.2, a region frequently affected by copy number variants in neurodevelopmental and neuropsychiatric disorders 1. The primary function of KCTD13 involves regulating RhoA protein degradation through proteasomal ubiquitination, which modulates actin cytoskeleton dynamics and synaptic transmission 23. KCTD13 deficiency impairs neural precursor proliferation and cortical development, with reduced neurite formation and diminished spontaneous neuronal network activity linked to ERBB signaling disruption rather than exclusive RhoA-dependent mechanisms 4. Gene dosage imbalances of KCTD13 contribute to genitourinary tract anomalies including hypospadias and cryptorchidism through altered androgen receptor subcellular localization and SOX9 expression 5. Notably, KCTD10-mediated degradation of KCTD13 is critical for proper brain development; KCTD10 deficiency causes neuronal progenitor abnormalities and reduced layer V neuron populations 6. KCTD13 copy number variants are significantly enriched in patients with genitourinary anomalies (2.58%) compared to controls (0.10%) 5. Therapeutically, targeting the RhoA pathway with ROCK inhibitors restores learning and memory deficits in KCTD13 and 16p11.2 deletion models 7, providing potential intervention strategies for associated neurodevelopmental disorders.