Schematic of RPA1’s role in telomere biology and relationship to other genes associated with TBD. RPA1, the largest subunit of the RPA heterotrimeric complex, binds single-stranded DNA (ssDNA) at telomeres. TBD-associated variants in RPA1 result in increased ssDNA binding affinity. The components of the telomerase enzyme complex (DKC1, TERC, TERT, NAF1, NOP10, NHP2), telomerase or hTR regulators (TCAB1, PARN, and ZCCHC8), and regulator of telomere elongation helicase 1 (RTEL1), are shown in green. Dark blue indicates the shelterin (TPP1, TIN2, and POT1) and CST (CTC1 and STN1) complexes. Protein names are shown. Gray symbols indicate known key telomere biology proteins not yet attributed to human disease (GAR1 in telomerase complex; TRF1, TRF2, and RAP1 in shelterin; and TEN1 in CST).