TRABD2B (TraB domain containing 2B) is a metalloprotease that functions as a negative regulator of Wnt signaling by cleaving the N-terminal region of specific Wnt proteins, including WNT3A and WNT5 1. Following cleavage, these Wnt proteins become oxidized and form inactive disulfide-bond oligomers, thereby suppressing Wnt pathway activation. The protein contains a conserved TIKI/TraB fold and exhibits Mn(2+)/Co(2+)-dependent catalytic activity 1. TRABD2B is required for proper head formation during embryonic development 2. Altered TRABD2B expression is implicated in multiple disease contexts. Hypomethylation of TRABD2B was identified in developmental language disorder (DLD), suggesting potential involvement in myelination disruption 3. Genetic variants in TRABD2B (rs1561573) show association with serum selenium deficiency and are functionally linked to thyroid hormone metabolism and Wnt pathway regulation 4. In complex disease associations, TRABD2B downregulation occurs in placental tissue from women with obstructive sleep apnea 5, and TRABD2B variants contribute to computer vision syndrome susceptibility through Wnt signaling modulation 6. Additionally, TRABD2B expression correlates with colorectal cancer prognosis in patients with slow transit constipation 7. These findings underscore TRABD2B's broader role in developmental, metabolic, and disease processes beyond canonical Wnt inhibition.