By combining hiPSC-derived neural and muscle cells, CRISPR-Cas9 genome editing, optogenetics, mask-position-controlled seeding and automated HCI analysis we were able to model ALS-related neuromuscular phenotypes and demonstrate a dose-dependent effect of the RIPK1 inhibitor, necrostatin-1, for rescuing disease phenotypes. Here, RIPK1 is linked to amyotrophic lateral sclerosis.