Molecular, biochemical, and evolutionary studies indicate that somatic angiotensin-converting enzyme (ACE) is developmentally regulated in a tissue-specific manner. However, many important questions remain unanswered. For example, the regulatory mechanisms that control the cell- and stage-specific expression of ACE remain largely unknown. The nature, location, and role of the enzyme involved in the release of plasma membrane-anchored ACE have not been elucidated. Although the expression and localization of ACE are developmentally regulated, the physiological implications of these changes in segmental nephron differentiation remain to be elucidated. Investigations of the cellular and molecular mechanisms mediating the developmental co-regulation of the renin-angiotensin and Kallikrein-kinin system by ACE are a formidable challenge for future research.