Replacement of charged and polar residues in the coiled-coiled interface of huntingtin-interacting protein 1 (HIP1) causes aggregation and cell death

► Charge repulsion in the HIP1 coiled-coil interface increases molecular plasticity.► Stabilized HIP1 aggregates into large particles. ► Stability mutations in HIP1 impact the immunoprecipitation of huntingtin. ► Presence of aggregated HIP1 causes cell death via necrotic and apoptotic pathways.