How does the intron-retained RNA isoform mechanistically reduce glucocerebrosidase protein levels and activity?

While the study shows the variant creates intron-retained transcripts that correlate with reduced enzyme activity, the precise molecular mechanism linking aberrant RNA to protein reduction is not explained. This mechanistic gap limits therapeutic target identification. Gap type: unexplained_observation Source paper: African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1. (2024, Nature structural & molecular biology, PMID:39668204)