Using cellular models that mimic the organization of the subtelomeric 4q35 locus found in patients affected with Facio-Scapulo-Humeral Dystrophy (FSHD) and in healthy individuals, we recently investigated the biological function of the D4Z4 macrosatellite within this domain. We demonstrated that D4Z4 acts as a CTCF and A-type Lamins dependent insulator element exhibiting both enhancer-blocking and barrier activities, and displaces a telomere towards the nuclear periphery. This peripheral positioning activity lies within a short sequence that interacts with CTCF and A-type Lamins. Depletion in either of these two proteins suppresses these perinuclear activities, revealing the existence of a subtelomeric sequence that is sufficient to position an adjacent telomere to the nuclear periphery. We discuss here the biological implications of these results in the light of our current knowledge in related fields and the potential implication of other CTCF and A- type lamins insulators in the light of human pathologies.