Muscleblind-like protein 1

Muscleblind-like protein 1 (MBNL1) is an RNA-binding protein that regulates pre-mRNA alternative splicing, functioning as both an activator and repressor depending on target sequence context (UniProt: Q9NR56). It binds consensus sequences including the characteristic YGCU(U/G)Y motif and expanded CUG repeats, thereby controlling splicing of genes such as cardiac troponin-T and insulin receptor. MBNL1 also coordinates vascular smooth muscle cell splicing events with other RNA-binding proteins.

MBNL1 is primarily known for its role in dystrophia myotonica type 1 (DM1), where expanded CUG repeats sequester the protein and disrupt normal splicing patterns (UniProt: Q9NR56). The protein is also associated with Fuchs endothelial corneal dystrophy. Its broader tissue distribution and splicing regulatory function suggest involvement in multiple organ systems.

In Alzheimer's disease, MBNL1 is upregulated in post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics), with a mean log₂ fold-change of 0.43 across measured subcellular fractions. This elevation may reflect altered RNA processing pathways in AD pathology, though the functional significance remains to be determined.