ZCCHC8 encodes a scaffolding subunit of the nuclear exosome targeting (NEXT) complex that plays critical roles in RNA surveillance and telomere maintenance. The protein functions as a scaffold mediating NEXT complex homodimerization while coordinating with MTR4 helicase and RBM7 to recognize and process aberrant transcripts and non-coding RNAs for exosomal degradation 1. ZCCHC8 regulates histone H3K27me3 levels by degrading nascent long non-coding RNAs containing G-quadruplex and U-rich motifs, which affects polycomb repressive complex 2 recruitment and gene silencing in cancer 2. The protein also forms functional connections with the Microprocessor complex through DGCR8 interaction, targeting miRNA precursor flanking regions 3. ZCCHC8 mutations cause telomere-related disorders including idiopathic pulmonary fibrosis and bone marrow failure syndromes. A novel P410A mutation disrupts nucleocytoplasmic localization, leading to decreased DKC1 and RTEL1 expression, shortened telomeres, and pulmonary fibrosis 4. Additional pathogenic variants have been identified in dyskeratosis congenita patients, demonstrating deficient ZCCHC8 function and inflammatory responses 5. The protein also negatively regulates type-I interferon responses by targeting IRF3 signaling, affecting RNA virus replication 6.