The β cells in the pancreatic endocrine islets preferentially secrete insulin in specific subdomains of the plasma membrane adjacent to the vasculature (i.e., hot spots). Impaired insulin secretion and β -cell dysfunction are central features of Type-2 Diabetes, yet the cytoskeletal machinery that supports directional secretion and secretory hot spots remains incompletely defined. KIF21A is a plus-end-directed kinesin-4 motor protein that anchors microtubule plus ends to the cell cortex. Our work introduces KIF21A as a disease-linked, mechanistically relevant motor whose distribution suggests a role in organizing secretion-competent cortical microtubule architecture in islet endocrine cells. We show that KIF21A is downregulated in T2D human islets at both the mRNA (RNA-seq) and protein (quantitative proteomics) levels. We also demonstrate cell-type-specific enrichment of Kif21a protein (δ > α > β) in intact islets, confirming the hierarchy suggested by single-cell transcriptomics. We also show that within each endocrine lineage, Kif21a protein shows pronounced cell-to-cell heterogeneity, consistent with endocrine sub-states and functional specialization. And most importantly, we show that implicating Kif21a is spatially enriched at the rosettes and laminin-rich interfaces at vasculature-oriented secretion sites (hot spots), where microtubule anchoring is expected to shape targeted granule delivery. These findings establish KIF21A as a T2D-associated gene in pancreatic endocrine cells and suggest that it may have a cortical microtubule-anchoring function and may contribute to the directed granule delivery to the vasculature for regulated hormone secretion.