TSHZ3 is a zinc-finger transcription factor that functions as a developmental regulator with roles in neural and urogenital development. As a transcriptional repressor, TSHZ3 recruits histone deacetylases HDAC1 and HDAC2 to regulate gene expression, particularly inhibiting CASP4 1. In brain development, TSHZ3 is highly expressed in cortical projection neurons (CPNs) and is required for proper corticostriatal circuit development and glutamatergic synaptic function 2. TSHZ3 controls neuronal specification in deep layer cortex 3 and regulates respiratory rhythm generators and nucleus ambiguus motoneurons critical for airway function. In urogenital development, TSHZ3 promotes smooth muscle differentiation in the proximal ureter through interaction with myocardin, positioning it downstream of BMP4 signaling 4. Clinically, heterozygous TSHZ3 deletions cause autism spectrum disorder (ASD) with ASD-like behavioral deficits and altered expression of glutamatergic synapse genes 52. Heterozygous TSHZ3 variants are associated with congenital anomalies of kidney and urinary tract (CAKUT), particularly multicystic dysplastic kidneys, hydronephrosis, and hydroureter 6. Additionally, TSHZ3 acts as a tumor suppressor in lung adenocarcinoma, where high expression correlates with better survival and suppresses epithelial-mesenchymal transition through M1 macrophage recruitment 7. These findings position TSHZ3 as a critical hub gene influencing neurodevelopmental and urogenital developmental pathways 8.