An acidic patch in the unstructured N‐terminus modulates <scp>LSD1</scp> activity

Lysine-specific demethylase 1 (LSD1) plays a crucial role in chromatin organization and gene regulation by removing methyl groups from histone and non-histone substrates. While its catalytic core is well characterized, the functional contributions of its intrinsically disordered N-terminal region remain less understood. Here, we identify a conserved acidic patch within this unstructured domain as a key regulator of LSD1 activity. Our findings suggest that this region influences enzymatic efficiency and interactions with regulatory cofactors, shedding new light on the mechanistic control of LSD1 function in epigenetic modulation.