There isn't necessarily a single "main thing" about the universe that science cannot explain, but there are several profound questions and mysteries that remain open and challenge our current scientific understanding. Some of these include:

1. **Dark Matter and Dark Energy:**

   - The majority of the mass-energy content of the universe is made up of dark matter and dark energy, both of which are mysterious and not yet directly observed. Their nature and properties are still unknown, and they constitute a significant portion of the universe.

2. **The Nature of Consciousness:**

   - The origin and nature of consciousness, self-awareness, and subjective experience remain topics of intense philosophical and scientific inquiry. While neuroscience has made significant strides, explaining the subjective experience of consciousness remains elusive.

3. **Quantum Mechanics and Gravity Unification:**

   - Unifying quantum mechanics, which describes the behavior of particles on a very small scale, with general relativity, which describes gravity on a large scale, remains a major challenge in theoretical physics. A complete theory of quantum gravity is yet to be established.

4. **Origin of the Universe:**

   - While the Big Bang theory provides a framework for the evolution of the universe, the exact origin of the universe and what, if anything, preceded the Big Bang is not yet fully understood.

5. **Quantum Entanglement and Non-locality:**

   - The phenomenon of quantum entanglement, where particles become correlated in ways that defy classical intuition, remains a puzzling aspect of quantum physics. The concept of non-locality challenges our understanding of space and time.

6. **Nature of Time:**

   - The nature of time, including whether time has a fundamental direction and what might have occurred before the Big Bang, is a topic of ongoing exploration and debate in physics and philosophy.

It's essential to recognize that science is a dynamic and evolving field. What may be currently unexplained or mysterious could become the subject of breakthroughs and new understanding in the future. The pursuit of knowledge involves constant questioning, exploration, and refinement of theories to better understand the complexities of the universe.