The finding that patients with Sjögren's syndrome exhibit a statistically significant increase in expression of BMP6 in the salivary gland, relative to healthy control subjects, is described. Also described is the finding that overexpression of BMP6 in the salivary glands of mice results in an increase in electrical potential across the salivary gland. Methods of diagnosing a subject as having Sjögren's syndrome, or at risk for developing Sjögren's syndrome, by measuring the level of BMP6 expression in a salivary gland of a subject, measuring electrical potential in a salivary gland of a subject, or both, are described. Methods of treating a subject with Sjögren's syndrome, or methods of increasing salivary flow in a subject, by administering an agent that inhibits BMP6 expression or activity are also described. The use of XIST and MECP2 as diagnostic and therapeutic targets for male Sjögren's syndrome patients is further described.