Suggested altered cellular pathways and their potential connection in PXE. The induction of cholesterol biosynthesis could lead to an increase in prenylation of small GTPases. Small GTPases are responsible for the activation of STAT3 and the Janus kinase (JAK)–STAT signal pathway. STAT3 could, thus, further upregulate p21, which in turn could induce cellular senescence and SA-β-Gal activity. Due to the development of a proinflammatory SASP, IL6 and MCP1 expression would increase and could further contribute to the induction of STAT3 and the JAK–STAT signal pathway. In addition to this, the induction of the cholesterol biosynthesis could lead to a reduction of LMNB1 gene expression under lipoprotein depleted conditions as a compensatory effect ABCC6: ATP-binding cassette sub-family C member 6; FPP: farnesylpyrophosphate; GPP: geranylpyrophasphate; GGPP: geranylgeranylpyrophosphate; HMG-CoA: 3-hydroxy-3-methyl-glutaryl-coenzyme A; HMGCR: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; IL6: interleukin 6; JAK–STAT: Janus kinase–signal transducer and activator of transcription; LMNB1: lamin B1; MCP1: monocyte chemoattractant protein-1; SA-β-Gal activity: senescence-associated-β-galactosidase activity.