CTSB and podoconiosis: Although the role of silica in the immunopathogenesis of podoconiosis is still unclear, it remains possible that silica (and/or other soil mineral) induces inflammation leading to the release of reactive oxygen species and apoptosis of cells52,53,58 which could lead to pathology through disruption of lysosomes and the upregulation of genes like MPO, CTSB, ITGA1, and BNIP3L which directly or indirectly shape the inflammation and the extracellular matrix.