rnaseq and flowcytometry of conventional scalp and palmoplantar psoriasis reveal shared and distinct molecular pathways it has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis however little is known about the molecular differences between scalp palmoplantar and conventional plaque psoriasis to investigate the molecular heterogeneity of these psoriasis subtypes we performed rnaseq and flow cytometry on skin samples from individuals with scalp palmoplantar and conventional plaque psoriasis along with samples from healthy control patients we performed differential expression analysis and network analysis using weighted gene coexpression network analysis wgcna our analysis revealed a core set of 763 differentially expressed genes common to all subtypes of psoriasis in contrast we identified 605 632 and 262 genes uniquely differentially expressed in conventional scalp and palmoplantar psoriasis respectively wgcna and pathway analysis revealed biological processes for the core genes as well as subtypespecific genes flow cytometry analysis revealed a shared increase in the percentage of cd4 t regulatory cells in all psoriasis subtypes relative to controls whereas distinct psoriasis subtypes displayed differences in il17a ifngamma and il22 production this work reveals the molecular heterogeneity of plaque psoriasis and identifies subtypespecific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque psoriasis