MAL2 (myelin and lymphocyte protein 2) is a tetra-transmembrane protein that functions as a component of polarized protein transport machinery in epithelial cells 1. Structurally, MAL2 localizes to membrane rafts and facilitates the indirect transcytotic route, mediating basolateral-to-apical protein transport via raft-dependent mechanisms involving redistribution from perinuclear endosomes 2. MAL2 interacts with multiple trafficking regulators including Rab17 and contains EVH1 recognition motifs that coordinate selective protein redistribution 3. Beyond canonical transport functions, MAL2 has emerged as a significant oncogene in multiple cancers. In intrahepatic cholangiocarcinoma, MAL2 directly interacts with EGFR to stabilize its membrane localization and activates the PI3K/AKT/SREBP-1 axis, promoting lipid accumulation and conferring cisplatin resistance 4. High MAL2 expression predicts poor prognosis in triple-negative breast cancer and ovarian cancer, correlating with increased proliferation, migration, invasion, and epithelial-to-mesenchymal transition 56. MAL2 is also a component of diagnostic signatures for pancreatic ductal adenocarcinoma detection in plasma extracellular vesicles 7. These findings position MAL2 as both a fundamental trafficking protein and a promising therapeutic target across malignancies.