Low L-selectin (CD62L) on CD4+ T cells after cryopreservation has been introduced in 2013 as a risk biomarker for the development of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment1 or HIV infection.2 The biomarker has been reproduced retrospectively in some international cohorts,3,4 but not in others,5 potentially because of its sensitivity to biomaterial quality, assay protocols, and the time point of testing. With regard to current approaches to PML risk reduction, natalizumab extended interval dosing is thought to improve immune surveillance and reduce PML risk, whereas clinical efficacy seems unaffected.6