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Achieving global biodiversity targets hinges on indicators of biodiversity change that convert raw data into reliable numbers that can shape policy, conservation, management, and, ultimately, the future of biodiversity worldwide. Indicators can only be used confidently if they detect and summarise biodiversity trends as intended, given the available data worldwide. Knowing whether indicators can reliably detect and summarize trends as intended requires robust testing, which is a challenging and under-developed practice. Here, we test the performance of a genetic diversity indicator of the Global Biodiversity Framework (GBF), the Proportion of populations with an effective size greater than 500 (or, Ne > 500) and show that it can be reliably reported under realistic scenarios of population trends, monitoring frequency, and observer error. To ensure this reliability, our results suggest that monitoring programs aim to monitor populations every 1 to 4 years, at least 40% of populations per species, and at least 8% (species pools of several thousands), 23% (species pools 300 to 500 species) or 56% (species pools <100) of the targeted species richness. These findings show that the indicator is, in addition to being feasible and meaningful, technically reliable under realistic biodiversity monitoring schemes. Going forward, it is still essential to invest in genetic monitoring using indicators as well as DNA-based data, particularly given the goal of safeguarding genetic diversity in the Global Biodiversity Framework. Beyond this indicator, we emphasize that performance testing is needed for more indicators to ensure reliable progress tracking towards the GBF targets and the global goal of halting biodiversity loss. • We address an urgent but overlooked need for rigorous testing of biodiversity indicators. • We find that populations should be monitored every 1 to 4 years for a reliable Ne > 500 indicator. • At least 40% of a species' populations should be monitored for a reliable species-level indicator. • At least 8% to 56% of species should be monitored for a reliable country-level indicator. • This approach can guide testing of other indicators for biodiversity conservation.