Amyotrophic lateral sclerosis (ALS) is an incurable disease of the motoric nervous system characterized by loss of function and degeneration of upper and lower motoneurons. Models resembling clinics are required to study pathomechanisms and validate therapeutic options in ALS. Here, we reprogrammed fibroblasts from ALS patient carrying a mutation in Fused in Sarcoma (FUS) gene into induced pluripotent stem cells (iPSCs). An isogenic iPSC line was generated to serve as a control. Doxycycline-inducible NIL-cassette was introduced for motoneuron differentiation. Motoneurons were analyzed for neurite length using IncuCyte imaging and Fiji. Membrane lactate dehydrogenase (LDH) leakage was measured over a period of 77 days and DNA damage was quantified using y-H2AX marker. Integrated stress response was assessed with qPCR and global translation with puromycin immunostaining. Deregulated transcripts and proteins were identified using RNA-sequencing and mass-spectrometry and validated with qPCR and Western blot. Motoneurons differentiated from inducible NIL-cassette containing iPSCs displayed neuronal morphology and expressed mature motoneuron markers. Neurite length between ALS patient and isogenic motoneurons did not differ. ALS motoneurons leaked more LDH from day 63 onwards (P<0.01), indicating lower survival, accumulated more DNA damage by day 42 of differentiation (P<0.01) and showed elevated expression of FGF21 and ADM2, suggesting increased integrated stress response. Puromycin staining, indicative of global translation, was weaker. We could identify deregulated transcripts and protein in ALS patient motoneuron neurites. We present an ALS model based on patient-derived motoneurons, which exhibit lower survival, higher DNA damage, presence of increased integrated stress response, deregulated transcripts and protein.