The MARVEL domain is a 130 amino acid motif that contains four transmembrane helices, both of which have cytoplasmic N- and C-terminal regions. MARVEL domain-containing proteins are thought to participate in tight junction regulation, the biogenesis of vesicular transport carriers and in cholesterol-rich membrane apposition events. MAL2 (mal, T-cell differentiation protein 2) is a 176 amino acid multi-pass membrane protein that is associated with lipid rafts and contains one MARVEL domain. Expressed predominately in liver, kidney and lung, MAL2 functions as a member of the polarized machinery transport system and is required for transcytosis, a transporter pathway used to deliver membrane-bound cargo from perinuclear endosomes to the apical surface in a raft-dependent manner. Differential expression of MAL2 is associated with several cancers, including renal cell carcinoma and childhood leukemia, suggesting a role for MAL2 in tumorigensis.