PMF1 (polyamine modulated factor 1) is a multifunctional protein involved in both nuclear and cytoplasmic processes. Primary functions include roles in kinetochore assembly and chromosome 1, with PMF1 localizing to the outer kinetochore as part of the MIS12/MIND complex 1, and transcriptional regulation through interactions with RNA polymerase II [GO annotations]. The protein is involved in polyamine homeostasis, an important regulator of cell growth and death 2. Mechanistically, PMF1 expression is regulated by DNA methylation, with hypermethylation of its promoter CpG island leading to transcriptional silencing 2. In bladder cancer, PMF1 hypermethylation is associated with loss of cytoplasmic protein expression 2. At the 1q22 locus, PMF1 expression is regulated through long-range promoter-enhancer chr1 interactions, and PMF1 overexpression may dysregulate polyamine catabolism 3. Clinically, PMF1 has significant disease relevance. In bladder cancer, PMF1 methylation is associated with tumor progression and poor overall survival in both univariate and multivariate analyses 24. PMF1 methylation in urinary specimens shows diagnostic potential (area under curve = 0.800) 2. Genetic variants at the PMF1 locus are associated with cerebral small vessel diseases, including non-lobar intracerebral hemorrhage and lacunar stroke 135, suggesting PMF1 as a potential therapeutic target for stroke prevention.