TASOR2 is the central scaffold component of the HUSH2 complex, a multiprotein epigenetic repressor distinct from the classical HUSH complex 1. HUSH2 assembles around TASOR2 and recruits shared subunits MPHOSPH8 and PPHLN1 to function as a core complex 1. Mechanistically, TASOR2-containing HUSH2 is recruited by the transcription factor IRF2 to interferon-stimulated genes, where it mediates transcriptional silencing through an H3K9me3-independent mechanism 1. This distinguishes HUSH2 from classical HUSH, which represses LINE-1 retroelements via H3K9me3-dependent mechanisms 1. HUSH and HUSH2 localize to distinct genomic loci, with HUSH2 specifically targeting KRAB-ZNFs and interferon signaling genes 2. Clinically, TASOR2 function is significant because competition between HUSH and HUSH2 for shared MPP8 and PPHLN1 subunits couples retroelement silencing with immune response induction 1. Dynamic regulation of TASOR2 expression enables cells to fine-tune epigenetic silencing of interferon genes, integrating genome defense mechanisms with innate immunity 2.