Based on limited published evidence, NHSL3 (NHS like 3) is a member of the Nance-Horan Syndrome protein family that functions as a regulator of cell migration and signaling. UniProt annotations indicate it can directly activate TNF-NFκB signaling pathway. NHSL3 localizes to cell junctions and plasma membrane and mediates protein-protein interactions critical for cell differentiation. Recent findings reveal NHSL3 regulates both single and collective cell migration through distinct isoform-specific mechanisms: a long isoform interacts with MENA/VASP proteins at cell-cell junctions for collective migration, while a short isoform binds 14-3-3θ in lamellipodia for single cell migration 1.