SLTM (SAFB like transcription modulator) is a nuclear chr15 and transcriptional regulator with dual DNA and RNA binding capacities. As a general transcriptional inhibitor, SLTM functions as an epigenetic silencing factor that suppresses gene expression, including HIV-1 latent provirus transcription 1. SLTM knockdown significantly increases HIV-1 reactivation (1.9-4.2 fold) and enhances chr15 accessibility at integrated HIV-1 loci, reducing inducible HIV-1-infected cell frequency by 62.2% in ex vivo CD4+ T cells from treated patients 1. Beyond viral latency, SLTM regulates metabolic and developmental pathways. SLTM participates in lipid accumulation regulation in adipocytes; CRISPR knockdown decreases lipid accumulation (fold change 0.51) 2, and rare damaging variants associate with body mass index and fat distribution traits across ancestries 3. SLTM also shows sex-dependent genetic effects on psychiatric disorders including schizophrenia, bipolar disorder, and major depressive disorder 4. In hepatocellular carcinoma, hypoxia-induced DTL ubiquitinates and degrades SLTM, relieving transcriptional repression of Notch1, thereby promoting cancer proliferation and sorafenib resistance 5. Additionally, SLTM interacts with RNA localization elements (SIRLOIN) alongside hnRNPK and SNRNP70 to regulate nuclear enrichment of long RNAs 6. Finally, SLTM variants show causal associations with male infertility through dysregulation in germ cells following endocrine disruptor exposure 7.