Multi-omics identifies RNF149 as a key molecular marker mediating neuron-glia interaction in temporal lobe epilepsy

Epilepsy is a complex central nervous system disease with a high incidence and a significant social health burden. Although there are many antiepileptic drugs, about 30% of patients are insensitive to existing drug treatments, and it is urgently required to identify reliable molecular markers and therapeutic targets. Traditional research has focused on a single omics level, and it is difficult to establish a complete connection from genetic variation to changes in cell function. In this study, a multi-level analysis framework integrating transcriptome, proteome, Mendelian randomization, and single-cell omics was constructed, and the E3 ubiquitin Ligase RNF149 was systematically screened and multi-dimensionally verified as a key candidate molecular marker for epilepsy. In external datasets (GSE88992, GSE127871, GSE255223) and animal models, RNF149 showed a stable trend of differential expression and was associated with hippocampal sclerosis and the severity of epileptic seizures. Single-cell communication investigation revealed that RNF149 may influence the pathological process of epilepsy by modulating the interaction between excitatory neurons and oligodendrocytes, particularly the NRG3-ERBB4 signaling axis. In conclusion, multi-omics integrated analysis highlighted RNF149's potential relevance as a molecular biomarker and treatment target for epilepsy, generating new ideas for precision diagnosis and mechanism research in temporal lobe epilepsy.