TOR1A, encoding the endoplasmic reticulum luminal protein torsinA, is involved in the endoplasmic reticulum stress response pathway [2]. It plays a significant role in the context of neurological disorders.

In a conditional knockout mouse model of Tor1a in the spinal cord and dorsal root ganglia, the mice recapitulated the phenotype of human DYT1-TOR1A dystonia, developing early-onset generalized torsional dystonia. This indicates that spinal neural circuits are part of the pathophysiological substrate of this form of dystonia [3].

Biallelic variants in TOR1A in humans cause autosomal-recessive TOR1A-related disorders, such as arthrogryposis multiplex congenita 5 (AMC5-TOR1A), which is characterized by severe congenital flexion contractures, variable developmental delay, motor symptoms, facial dysmorphism, and a range of neuroimaging features [1].

In conclusion, TOR1A is crucial in the endoplasmic reticulum stress response pathway. The Tor1a conditional knockout mouse model has provided insights into the pathophysiology of DYT1-TOR1A dystonia. Human studies of biallelic TOR1A variants have expanded our understanding of the clinical and genetic spectrum of related autosomal-recessive diseases, highlighting its importance in neurodevelopmental and neurodegenerative disorders.