CDC50B (cell division cycle 50 P4-ATPase accessory subunit B) is a two-transmembrane-spanning accessory protein that functions as a β-subunit of P4-ATPase phospholipid flippase complexes 1. CDC50B mediates the export of specific P4-ATPase alpha subunits (ATP8B1, ATP8B2) from the endoplasmic reticulum to the plasma membrane, enabling their proper subcellular localization and enzymatic activity 2. The protein interacts selectively with certain P4-ATPases; ATP8B1 and ATP8B2 co-immunoprecipitate with both CDC50A and CDC50B, while other P4-ATPases associate exclusively with CDC50A 2. CDC50B is essential for the stable assembly and catalytic function of P4-ATPase complexes that transport aminophospholipids from the outer to inner membrane leaflets, maintaining asymmetric phospholipid distribution 3. In disease contexts, CDC50B dysfunction contributes to impaired P4-ATPase activity; mutations in ATP8B1 partners cause intrahepatic cholestasis, and structural analysis reveals CDC50B participates in P4-ATPase activation 4. CDC50B expression is tissue-specific, detected in pancreatic, renal, and prostate tissues, and upregulated in various malignancies 1. These accessory functions highlight CDC50B's critical role in maintaining cellular membrane integrity and lipid-dependent signaling processes.