In this lecture I will review our current understanding of the pathogenic pathways important in IgA nephropathy and discuss how this knowledge is being leveraged to deliver novel therapeutic approaches to the treatment of IgA nephropathy. Central to the pathogenesis of IgA nephropathy is the presence of excess IgA1 O-glycoforms with low levels of O-linked galactose in the IgA1 hinge region. These IgA1 O-glycoforms are predominantly polymeric and are likely derived from mucosally primed B cells. There is extensive evidence supporting a mucosal origin for this poorly O-galactosylated IgA1 and that the gut associated lymphoid tissue is the likely major source of this pathogenic form of IgA1. The presence of increased levels of polymeric poorly O-galactosylated IgA1 in the circulation is the precipitant for the formation of high molecular weight IgA-containing immune complexes which have the propensity to deposit in the glomerular mesangium and trigger glomerular inflammation. These IgA-containing immune complexes contain a wide variety of protein constituents, many of which have pro-inflammatory activity. Formation of immune complexes in IgA nephropathy is incompletely understood but likely involves polymeric IgA1 self aggregation and an interaction with IgG antibodies with specificity for the Ig1 hinge region. These IgG antibodies may be “true” autoantibodies or microbial-specific IgG antibodies that cross react with poorly O-galactosylated polymeric IgA1. Deposition of IgA-containing immune complexes in the glomerular mesangium does not invariably trigger inflammation and it is poorly understood what factors determine whether mesangial IgA deposition is benign or pro-inflammatory. In those cases where glomerular injury is triggered the principal cell driving this response is the mesangial cell. Mesangial cell proliferation and mesangial cell derived pro-inflammatory and pro-fibrotic factors drive recruitment of monocyte/macrophages into the glomerulus and, following their passage across the glomerular basement membrane, trigger podocyte injury and activation of tubular epithelial cells. These effects are amplified by simultaneous passage of IgA-containing immune complexes across the glomerular basement membrane, which is amplified with progressive inflammation-induced damage to this permselective barrier. There is an increasing recognition that activation of the complement system plays a significant role in driving an inflammatory response within both the glomerulus and tubulointerstitium. The kidney response to mesangial IgA deposition appears to be under significant epigenetic control, with recent reports highlighting the importance of microRNA dysregulation in both the inflammatory and fibrotic responses to IgA deposition. Our evolving understanding of key pathogenic pathways operating in IgA nephropathy has led to a rapid expansion in the number of novel therapies being evaluated in IgA nephropathy which will be reviewed by Professor Hong Zhang.