Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis involving the folds with lentiginous hyperpigmentation and reddish-brown papules. Four main types of DDD have been implicated with variable clinical presentation likely related to the heterogeneity of the gene variant landscape. Pathogenic Keratin 5 (KRT5) gene variants favour a reticular distribution with predominant fold involvement, whereas pathogenic variants in POGLUT1 lead to a widespread form with acantholytic features previously named Galli-Galli disease, now belonging to the disease spectrum of DDD and renamed DDD type 4. This study details the clinical and histopathological features associated with the heterozygous variant c.205C>T, p.(Arg69*) in POGLUT1 of two families from northern Italy affected by DDD4. Despite sharing the same variant, clinical manifestations varied among the affected members of the two families. Environmental factors probably contribute to phenotypic variability and symptoms exacerbation. Histopathology was substained by digitiform rete ridges, suprabasal acantholysis and dyskeratosis. Moreover, we detected aberrant KRT5 expression in two biopsies. A review of the literature on POGLUT1-related DDD subtypes contextualizes these findings. The fact, that several patients have been reported to carry the variant c.205C>T, p.(Arg69*) might point to a potential mutational hotspot.