Mobp, short for myelin-associated oligodendrocyte basic protein, is a relatively abundant CNS-specific myelin protein. It plays a crucial role in stabilizing the myelin sheath in the central nervous system (CNS), which is essential for the rapid saltatory conduction of action potentials within the CNS and for sustaining neuronal health [3]. The non-receptor tyrosine kinase Fyn regulates MOBP synthesis, and MOBP affects the morphological differentiation of oligodendrocytes [6].

Genetic studies suggest that a locus between RPSA and MOBP may contribute to an increased risk of sporadic frontotemporal dementia (sFTD) through effects on gene expression and/or splicing in the brain cortex [1]. In multiple system atrophy (MSA), MOBP mRNA levels decrease, correlated with increased DNA methylation, and MOBP mislocalizes into glial cytoplasmic inclusions where it interacts with α-synuclein, indicating its relevance to MSA pathogenesis [2]. In multiple sclerosis (MS), MOBP is considered a primary target autoantigen, with T-cell autoimmunity against it detectable in patients [3]. However, MOBP-specific cellular immune responses are weaker than MOG-specific ones in MS patients and healthy subjects [7]. In a Greek population, the rs616147 polymorphism of MOBP was not associated with amyotrophic lateral sclerosis (ALS) [4]. Neonatal antibiotic-induced gut dysbiosis led to increased expression of MOBP and other myelin-related genes in the pre-frontal cortex of mice, affecting the microbiota-gut-brain axis [5]. Inhibiting MOBP expression blocked the long-lasting antidepressant effects of ketamine, suggesting its role in myelination-related antidepressant mechanisms [8]. A genome-wide association study identified a region near MOBP associated with non-viral HCC in European descent populations from North America [9].

In conclusion, Mobp is essential for myelin sheath stability and oligodendrocyte morphological differentiation. Its dysregulation is implicated in various neurodegenerative diseases such as sFTD, MSA, and MS, as well as in non-neurological conditions like HCC. Functional studies, including those using potential genetic models, have provided insights into its role in these disease processes, helping to understand the underlying molecular mechanisms and potentially guiding future therapeutic strategies.