PROX2 is a transcription factor belonging to the prospero-related homeobox gene family that functions as a transcriptional activator 1. As a DNA-binding transcription factor, PROX2 regulates RNA polymerase II-mediated transcription through sequence-specific binding to cis-regulatory regions in chr14. The N-terminal region of PROX2 contains an activation domain critical for its transcriptional regulatory function 1. During development, PROX2 is expressed in defined structures of the central nervous system and eye, as well as in postnatal eyes and adult testes 21. Unlike its homolog PROX1, which is essential for embryogenesis and retinal horizontal cell differentiation, PROX2 is dispensable for normal embryonic development, eye development, and male fertility, as demonstrated by studies of PROX2 knockout mice that developed without overt abnormalities 1. Notably, PROX2 has been identified as a high-confidence, potentially causal genetic risk gene for major depression in transcriptome-wide association studies, representing one of six strongly colocalized associations with depression susceptibility 3. This implicates PROX2 in neuronal and synaptic processes relevant to psychiatric disease pathogenesis.