VWA2 (von Willebrand factor A domain containing 2) encodes AMACO, a secreted protein that plays significant roles in colorectal cancer progression and immune evasion. The protein contains a von Willebrand factor A domain and functions in protein binding, cell-matrix adhesion, and basement membrane organization 1. VWA2 is dramatically overexpressed in approximately 78% of colorectal carcinomas with an average fold change >15, making it a promising biomarker for this cancer type 1. Mechanistically, VWA2 promotes colorectal cancer cell invasion and migration by inhibiting natural killer (NK) cell activation, upregulating immunosuppressive factors while downregulating pro-inflammatory responses 2. The protein's overexpression correlates with MYC and MYC-target gene expression, suggesting it participates in a MYC-driven oncogenic program 1. In kidney development, VWA2 localizes to basement membranes of ureteric bud and metanephric mesenchyme derivatives, interacting with the Fraser complex component FRAS1 3. Disease-wise, homozygous missense mutations in VWA2 are associated with vesicoureteral reflux 3 and may contribute to Alzheimer's disease risk in sporadic patients 4. The gene shows potential as both a biomarker and therapeutic target, particularly in colorectal cancer where it represents tumor aggressiveness and immune evasion mechanisms.