C9orf72, located on chromosome 9, encodes a 54-kDa protein with functions in multiple cellular processes such as autophagy, membrane trafficking, and immune response [3,4,5]. It forms a complex with SMCR8 and WDR41, potentially acting as a GTPase activating protein [3]. The hexanucleotide (G4C2) repeat expansion in C9orf72 is the major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) [1,2,3,4,5,6,7,8].

In mice, C9orf72 deficiency results in exaggerated inflammatory responses, indicating its role in regulating inflammatory outputs. Human patients with C9orf72 mutations also show a neuroinflammation phenotype. This suggests that C9orf72 may regulate trafficking and lysosomal degradation of inflammatory mediators like toll-like receptors (TLRs) and STING [5].

In conclusion, C9orf72 is crucial in multiple cellular processes and immune regulation. Studies on C9orf72 knockout or conditional knockout mouse models have provided insights into its role in the pathogenesis of ALS and FTD, highlighting its importance in understanding the mechanisms of these neurodegenerative diseases [5].