PLEKHB2 (pleckstrin homology domain containing B2) is a membrane-associated protein involved in retrograde transport of recycling endosomes. The protein contains a pleckstrin homology domain that mediates phosphatidylinositol lipid binding, positioning it to regulate endosomal trafficking pathways 1. PLEKHB2 functions in coordination with other recycling endosomal proteins to maintain proper membrane trafficking between the trans-Golgi network and recycling endosomes 2. In cancer biology, PLEKHB2 has emerged as a functionally relevant gene in colorectal carcinoma. Alternative splicing of PLEKHB2 pre-mRNA is regulated by the RNA-binding protein hnRNPM, which directly binds exon 9 of PLEKHB2 to facilitate skipping of alternative exon 8. The PLEKHB2-S splice isoform promotes colon cancer cell proliferation both in vitro and in vivo 3. Additionally, PLEKHB2 was identified as one of nine genes whose baseline expression levels predict influenza vaccination response magnitude in young individuals 4. Clinically, PLEKHB2 is located within a 2q21.1 microdeletion region associated with developmental delay, intellectual disability, ADHD, and neurological abnormalities 5, 6. PLEKHB2 expression is reduced in left-sided versus right-sided colon carcinoma, suggesting differential roles in anatomically distinct tumor subtypes 7.