First, the pathologic lesion of endocapillary proliferation is associated with a higher risk of progressive loss of renal function, and second, it is potentially modifiable by corticosteroid therapy. Large observational studies suggest that corticosteroids may be effective in preventing progression of IgAN. However, corticosteroids have broad cellular and biologic effects with significant toxicity. Identification of the specific molecules and pathways upregulated in endocapillary proliferation and potentially modulated by corticosteroids may yield information for development of more targeted therapy focused on the downstream genes and proteins regulated by NFkB. Our first finding is that in the isolated microdissected glomeruli of human diagnostic kidney biopsies, endocapillary proliferation is associated with a distinct signature of differentially expressed mRNA transcripts. We identified the biologic processes and pathways represented in this signature, using canonical pathway analysis. Given that endocapillary proliferation may be amenable to therapy with corticosteroids and that the prime mechanism of action of this drug is interruption of NFkB-mediated gene transcription, we verified that our signature includes transcripts regulated by this transcription factor. Indeed one-third of the transcripts contain upstream promoter binding sites. Finally, we employed in silico drug screening and confirmed that the endocapillary proliferation transcriptome is alpha-Mangostin significantly enriched with pathways modulated by corticosteroids, which is supportive of clinical observations of efficacy of corticosteroids in patients with this lesion. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for treatment of IgAN. The Epimedoside-A glomerular mRNA expression profile associated with endocapillary proliferation includes a significant number of transcripts encoding proteins involved in the innate immune response, such as several toll-like receptors. One of the potential mechanisms hypothesized to be responsible for development of IgAN is a dysregulated immunologic response to a mucosal microbial challenge.