APPL (Adaptor Protein containing PH domain, PTB domain, and Leucine zipper motif) antibodies target a family of intracellular adaptor proteins, primarily APPL1 and APPL2. which play critical roles in signal transduction and membrane trafficking. Discovered in the early 2000s, APPL proteins interact with multiple signaling pathways, including those mediated by Akt, Rab5. and G-protein-coupled receptors, influencing cell survival, proliferation, and glucose metabolism. APPL1. the better-characterized isoform, links insulin signaling to adiponectin receptors, impacting metabolic homeostasis. Its dysfunction is implicated in diabetes, obesity, and cancer. APPL2 shares structural similarity but exhibits distinct functions, such as regulating endosomal trafficking and neuronal development. Antibodies against APPL proteins are essential tools for studying their localization, expression levels, and interactions in various tissues. They enable detection via Western blotting, immunofluorescence, and immunohistochemistry, aiding research into metabolic disorders, neurodegenerative diseases, and oncogenesis. Recent studies also explore APPL's role in autophagy and immune responses, expanding its relevance in biomedical research. Commercial APPL antibodies are typically validated for specificity using knockout cell lines or siRNA knockdowns, ensuring reliability in experimental models.