Scavenger receptor class B member 2 (SCARB2) (also called LIMP-2, CD36L2 or LGP85) is a major ly-sosomal membrane glycoprotein involved in en-dosomal and lysosomal biogenesis and maintenance. SCARB2 acts as a receptor for the lysosomal mannose-6-phosphate independent targeting of ߭glucuronidase and enterovirus 71 and influences Parkinson's disease and epilepsy. Genetic deficiency of this protein causes deafness and peripheral neuropathy in mice as well as myoclonic epilepsy and nephrotic syndrome in hu-mans. Comparative SCARB2 amino acid sequences and structures and SCARB2 gene locations were exam-ined using data from several vertebrate genome pro-jects. Vertebrate SCARB2 sequences shared 43-100% identity as compared with 30-36% sequence identities with other CD36-like superfamily members, SCARB1 and CD36. At least 10 N-glycosylation sites were con-served among most vertebrate SCARB2 proteins ex-amined. Sequence alignments, key amino acid residues and conserved predicted secondary structures were examined, including cytoplasmic, transmembrane and external lysosomal membrane sequences: cysteine di-sulfide residues, thrombospondin (THP1) binding sites and 16 proline and 20 glycine conserved residues, which may contribute to short loop formation within the exomembrane SCARB2 sequences. Vertebrate SCARB2 genes contained 12 coding exons. The human SCARB2 gene contained a CpG island (CpG100), ten microRNA-binding sites and several transcription fac-tor binding sites (including PPARA) which may con-tribute to a higher level (2.4 times average) of gene expression. Phylogenetic analyses examined the rela-tionships and potential evolutionary origins of the ver-tebrate SCARB2 gene with vertebrate SCARB1 and CD36 genes. These suggested that SCARB2 originated from duplications of the CD36 gene in an ancestral genome forming three vertebrate CD36 gene family members: SCARB1, SCARB2 and CD36.