We demonstrate that K277E does not impair the ubiquitin-binding activity of NEMO; instead, it disrupts the HOIP–NEMO interface, destabilizes linear ubiquitin chain assembly complex (LUBAC) engagement in TNFR1 complex I, reduces linear ubiquitination, and promotes RIPK1 activation. We further identify a linked regulatory layer centered on inducible ubiquitination of NEMO at K285 that functions as a checkpoint restraining RIPK1.