MRPL33 encodes a large subunit protein of the mitochondrial ribosome involved in mitochondrial translation 1. The gene produces two isoforms through alternative splicing: the long form (MRPL33-L) containing exon 3 and the short form (MRPL33-S) lacking exon 3, with distinct functional roles 2. MRPL33-L depletion impairs mitochondrial function, increasing reactive oxygen species accumulation and decreasing ATP production and 16S rRNA levels 1. In cancer biology, MRPL33-L promotes tumor cell proliferation and survival. Its splicing is regulated by hnRNPK and RBM39 in different cancer types; elevated MRPL33-L inclusion correlates with enhanced tumorigenicity in colorectal and gastric cancers 1 3. Conversely, MRPL33-S promotes chemosensitivity to epirubicin in gastric cancer by deactivating PI3K/AKT signaling 2. Beyond cancer, MRPL33 shows dysregulated expression in diverse conditions: reduced expression in congenital hypothyroidism associates with impaired thyroid function via IL-2/STAT5 pathways 4, elevated levels protect against primary biliary cholangitis 5, and altered expression correlates with tuberculosis progression 6. These findings establish MRPL33 as a multi-functional biomarker whose isoform composition and expression levels influence mitochondrial function, immune regulation, and disease progression across multiple pathologies.