RBPJL (recombination signal binding protein for immunoglobulin kappa J region like) is a transcription factor that plays critical roles in pancreatic development and bone formation. As a component of the PTF1 transcriptional complex, RBPJL cooperates with PTF1A and E proteins to regulate pancreatic acinar cell specification and maintenance 1. RBPJL is essential for exocrine pancreas development, as demonstrated by its reduced activity during acinar-to-ductal metaplasia, a precancerous transformation 2. In bone remodeling, the Fam102a-Rbpjl axis facilitates nuclear translocation of transcription factors and promotes Osterix expression, which is essential for osteoblast differentiation; loss of functional RBPJL leads to osteopenia 3. RBPJL is pancreas-enriched and regulates expression of exocrine enzymes including CTRB and CEL 4. A population-specific p.(Thr280Met) variant in RBPJL associates with type 2 diabetes risk in Amerindian populations by reducing protein stability and impairing transactivation of exocrine enzyme promoters 5. Recent genomic studies identify RBPJL mutations as subtype-specific risk factors in frontotemporal lobar degeneration with TDP-43 pathology, suggesting roles in neurodegeneration 6. RBPJL expression is also elevated in specific pancreatic cancer subtypes 7.