Corticosteroids Paederosidic-acid modulate activity of several transcription factors, and their main effects on immune responses are ascribed to inhibition of the activity of nuclear factor k-B. Unfortunately, due to the protean cellular effects of corticosteroids, this therapy is associated with a broad range of toxicity, therefore more targeted treatment options that influence development of endocapillary proliferation are urgently needed. To determine the molecular pathways Gomisin-G involved in the development of endocapillary proliferation in patients with IgAN, and to identify novel therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from patients with IgAN. We compared the mRNA expression profile of biopsies with glomerular endocapillary proliferation to biopsies without endocapillary proliferation, based upon interpretation by three independent nephropathologists. We then identified the mRNA transcriptomic profile associated with the pathologic finding of endocapillary proliferation in IgAN. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is enriched with pathways modulated by corticosteroid exposure. With this approach we also identified new therapeutic targets that may be responsible for the pathogenesis of this lesion, and a panel of small molecules that may be candidates for modulation of the pathways responsible for development of endocapillary proliferation. Taken together, our findings are proof of principle that evaluation of the human tissue molecular phenotype associated with a distinct, clinically important and carefully annotated pathologic phenotype can yield insights regarding novel therapeutic strategies for the treatment of IgAN. We have employed a translational approach to delineate molecular mechanisms underlying the development of endocapillary proliferation in human subjects with IgAN, and to identify potential therapeutic targets to modulate this disease. Our approach to identification of clinically and biologically relevant processes involved in progressive IgAN was based upon two important clinical observations.