Heterogeneous nuclear ribonucleoprotein L

Heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a splicing factor that binds to CA-rich exonic or intronic elements to modulate exon inclusion as either an activator or repressor (UniProt: P14866). It functions as a component of hnRNP complexes associated with nascent transcripts and participates in transcriptional regulation; notably, it forms ribonucleoprotein complexes with ZNF827, HNRNPK, and circZNF827 that may suppress genes involved in neuronal differentiation and regulates alternative splicing of neuronal differentiation genes through H3K36me3-coupled mechanisms.

HNRNPL is implicated in Alzheimer's Disease pathology. In human post-mortem AD brain compared to age-matched controls, HNRNPL was consistently upregulated across subcellular fractions (mean log2 fold-change: 0.39) in TMT-labeled proteomics analysis (Chaparral AD proteomics). This upregulation suggests altered RNA processing and splicing activity may contribute to AD-associated pathology. The protein's established role in neuronal differentiation and transcriptional control indicates potential relevance to neurodegeneration mechanisms in AD.