NAF1 is an RNA-binding protein essential for ribosomal biogenesis and telomere maintenance. Functionally, NAF1 assembles box H/ACA small nucleolar ribonucleoproteins (snoRNPs) by associating with nascent complexes and facilitating their maturation, eventually being replaced by NOLA1/GAR1 [UniProt annotation]. It also stabilizes telomerase RNA and promotes telomerase holoenzyme assembly through competitive binding with DKC1 [UniProt annotation]. NAF1 participates in snoRNA-guided pseudouridine synthesis of ribosomal RNA [GO annotations]. NAF1 mutations cause telomere biology disorders (TBDs), a group of rare diseases characterized by impaired telomere maintenance 1. Patients harboring loss-of-function NAF1 mutations present with diverse clinical manifestations, predominantly bone marrow failure, aplastic anemia, pulmonary fibrosis, and liver cirrhosis 1. NAF1 mutations are identified in approximately 30% of familial interstitial lung disease (ILD) cases, where they associate with accelerated decline in lung function 2. Additionally, NAF1 variants (rs4691896) significantly increase susceptibility to coal workers' pneumoconiosis in Chinese populations 3. NAF1 mutations are also implicated as probable causes of early-onset emphysema 4. Beyond pulmonary disease, NAF1 dysregulation contributes to colorectal cancer development; reduced NAF1 expression correlates with more aggressive tumor phenotypes 5. NAF1 additionally regulates HIV-1 latency by suppressing viral LTR-driven transcription in CD4+ T cells 6, identifying it as a multifunctional protein bridging ribosomal biogenesis, telomere homeostasis, and viral persistence.